Oncogenes have become the central concept in understanding cancer biology and may provide valuable targets for therapeutic drugs. In many types of human tumors, including lymphomas and leukemias, the oncogenes are overexpressed, and may be associated with tumorigenicity (Tsujimoto et al., Science 228:1440-1443 (1985)). For instance, high levels of expression of the human bcl-2 gene have been found in all lymphomas with a t(14; 18) chromosomal translocations including most follicular B cell lymphomas and many large cell non-Hodgkin's lymphomas. High levels of bcl-2 gene expression have also been found in certain leukemias that do not have a t(14; 18) chromosomal translation, including most cases of chronic lymphocytic leukemia acute, many lymphocytic leukemias of the pre-B cell type, neuroblastomas, nasopharyngeal carcinomas, and many adenocarcinomas of the prostate, breast and colon. (Reed et al., Cancer Res. 51:6529 [1991]; Yunis et al., New England J. Med. 320:1047; Campos et al., Blood 81:3091-3096 [1993]; McDonnell et al., Cancer Res. 52:6940-6944 [1992); Lu et al., Int. J. Cancer 53:29-35 [1993]; Bonner et al., Lab Invest. 68:43A [1993]. Other oncogenes include TGF-α, c-ki-ras, ras, Her-2, and c-myc.
The expression of oncogenes may be inhibited by single stranded DNAi oligonucleotides. Nucleic acid therapeutics, however, often lack therapeutic efficacy due to instability in body fluids or inefficient uptake into cells.
There is therefore a need for a stable and efficient delivery of such DNAi oligonucleotides in body fluids and cells for the treatment of cancer.